Quaternary ammonium compounds

Abstract

The invention features quaternary ammonium compounds of formula I, described herein, and their use in treating asthma, chronic obstructive pulmonary disorder, allergic rhinitis, and infectious rhinitis.

1. A quaternary ammonium compound of formula I 
                 
 and any stereoisomers thereof, wherein  
 R 1  is selected from C 1 -C 6  alkyl, —CH 2 —(C 1 -C 4  alkenyl), and —CH 2 —(C 1 -C 6  alkynyl), each of which is optionally substituted with a group selected from phenyl, C 1 -C 4  alkoxy, and hydroxyl;  
 R 2  is selected from H or OH; and  
 
       X represents an anion of a pharmaceutically acceptable acid. 
     
     
       2. The compound of  claim 1 , wherein X is selected from the group consisting of the anions of the following acids: tartaric, hydrochloric, hydrobromic, hydroiodic, sulfuric, phosphoric, nitric, citric, methanesulfonic, CH 3 —(CH 2 ) n —COOH where n is 0-4, HOOC—(CH 2 ) n —COOH where n is 1-4, HOOC—CH═CH—COOH, and benzoic. 
     
     
       3. The compound of  claim 1 , wherein X is selected from the group consisting of iodide, bromide, and chloride. 
     
     
       4. The compound of  claim 1 , wherein X is iodide. 
     
     
       5. The compound of  claim 1 , wherein X is bromide. 
     
     
       6. The compound of  claim 1 , wherein X is chloride. 
     
     
       7. The compound of  claim 1 , wherein R 1  is methyl. 
     
     
       8. A compound (2R)-N-[1-(6-aminopyridin-2-ylmethyl)1-methylpiperdin-4-yl]-2-[(1R)-3,3,-difluorocyclopentyl]-2-hydroxy-2-phenylacetamide iodide. 
     
     
       9. A pharmaceutical composition comprising a pharmaceutical carrier and a therapeutically effective amount of a quaternary ammonium compound of formula I 
                 
 and any stereoisomers thereof, wherein  
 R 1  is selected from C 1 -C 6  alkyl, —CH 2 —(C 1 -C 4  alkenyl), and —CH 2 —(C 1 -C 6  alkynyl), each of which is optionally substituted with a group selected from phenyl, C 1 -C 4  alkoxy, and hydroxyl;  
 R 2  is selected from H or OH; and  
 
       X represents an anion of a pharmaceutically acceptable acid. 
     
     
       10. The method of treating a mammal for asthma, Chronic Obstructive Pulmonary Disease, allergic rhinitis, and infectious rhinitis, comprising: 
       administering a therapeutically effective amount of a quaternary ammonium compound of formula I, having the structure 
                 
 and any stereoisomers thereof, wherein  
 R 1  is selected from C 1 -C 6  alkyl, —CH 2 —(C 1 -C 4  alkenyl), and —CH 2 —(C 1 -C 6  alkynyl), each of which is optionally substituted with a group selected from phenyl, C 1 -C 4  alkoxy, and hydroxyl;  
 R 2  is selected from H or OH; and  
 
       X represents an anion of a pharmaceutically acceptable acid.